Maternal Prenatal Heavy Metal Exposures and Indices of Neonatal Brain Development: Moderations by Maternal Psychosocial Stressors

• In Event: From psychological to environmental risk mechanisms: Advancing the study of prenatal influences on biobehavioral development

Abstract

Background: Prenatal stressors from the physical [e.g. heavy metals (HMs)] and social (e.g. economic strain) environments may commonly activate maternal endocrine and immune systems, increasing oxidative stress and inflammation, which can have downstream effects on fetal development (Madrigano et al., 2012). To date, studies have found that exposure to maternal prenatal HMs are associated with child developmental deficits (e.g. Freire et al., 2018). However, few studies have examined the relationships between prenatal HM exposure and infant neurodevelopment as an early indicator of later outcomes. Additionally, there is evidence that psychosocial stressors may act synergistically with HMs to affect offspring outcomes (e.g. Stroustrup et al, 2016). We examined associations between maternal prenatal HM exposures and interactions between HMs and psychosocial stressors on indices of neonatal neurodevelopment.

Methods: In mid-pregnancy, participants (N=184) provided a urine sample and completed questionnaires. Urine samples from 94 participants have been assayed for HMs including arsenic, lead, cadmium, and manganese; the remaining samples will be assayed in December 2020. Neonates (N=104) were scanned at 2 weeks using 3T MRI. Hemispheric-specific volumes were estimated for the thalamus, hippocampus, cerebellum, amygdala, and frontal lobes using UNC NIRAL and Royal Alberts pipelines. Economic strain (Marshall et al. 2020) and depressive symptoms (Munoz-Rocha et al. 2018) have been previously found to moderate the effect of HMs on child development. Using multiple linear regressions and adjusting for covariates, we first examined the main effects of the four HMs and these two stressors on each brain volume. We added interaction terms for each prenatal HM x stressor (e.g. arsenic x economic strain) to models; interactions that were statistically significant (alpha=0.05) were probed.

Results: Only the main effect of prenatal lead exposure was associated with right hippocampal volume (B=-0.52, p=0.001). While we found no main effects for other prenatal HMs and psychosocial stressors, we identified three patterns of interactions, such that the effects of prenatal exposure to manganese, cadmium, and arsenic on infant brain volumes was moderated by maternal depressive symptoms or economic strain. First, maternal depressive symptoms were associated with smaller bilateral cerebellum and frontal lobe volumes if mothers also had prenatal exposure to manganese. Second, maternal economic strain was associated with smaller left cerebellum, hippocampus, and frontal lobe volumes if mothers also had prenatal exposure to cadmium. Finally, maternal economic strain and depressive symptoms were associated with smaller bilateral thalamic volumes if mothers also had higher prenatal exposure to arsenic.

Conclusion: We found evidence that the effects of prenatal maternal heavy metal exposures on infant neurodevelopment is moderated by other psychosocial stressors (and vice versa). Psychosocial stressors, such as depressive symptoms or economic strain, may compromise biologic systems, increasing the vulnerability to environmental stressors, including HMs (Wright, 2009). The results of this study support the need to consider how exposures to stressors across physical and social environments during pregnancy may synergistically affect offspring development. This is particularly important when considering health and developmental disparities, as children from poor households may be more likely to experience both prenatal physical and social stressors.

Authors

• Amanda Wylie, University of North Carolina at Chapel Hill
  Presenting Author

• Cathi Propper, University of North Carolina at Chapel Hill
  Non-Presenting Author

• Michael T. Willoughby, RTI International
  Non-Presenting Author

• Marie Camerota, Brown University
  Non-Presenting Author

• Sarah J Short, University of Wisconsin - Madison
  Non-Presenting Author